A long-term goal of my research is to elucidate the molecular mechanisms that control axon guidance in the developing mammalian central nervous system (CNS). The mechanisms regulating the pathfinding events of vertebrate motor neurons are not well understood, primarily due to the lack of appropriate cell surface markers with which to identify specific classes of spinal motor neurons and their axons. The molecular mechanisms that regulate the directionality of motor axon outgrowth must be understood prior to developing therapies designed to repair damage caused by disease or injury. Monoclonal antibody (mAb) SAC1 was recently identified as a specific marker of a small, bilaterally-symmetric population of motor neurons in the embryonic rat ventral spinal cord. Uniquely, this subset of motor neurons, referred to as spinal accessory motor neurons (SACMN), extend dorsally-projecting axons that innervate a small number of muscle groups in the neck. The specificity of mAb SAC1 allows for experiments to be performed that may elucidate the molecular mechanisms governing their guidance. Thus, the results of the proposed studies are directly relevant to the design of strategies aimed at restoring motor control in diseased or injured individuals. I propose to determine the spatiotemporal distribution of mAb SACl-positive motor neurons/axons in the developing rat and mouse CNS and identify attractive/repulsive molecules that regulate the growth of mAb SACl-positive axons in vitro. In addition, I will determine whether the floor plate plays a significant role in regulating the trajectory of spinal accessory motor axons in vivo, and characterize the distribution of the mAb SAC1 antigen in the CNS of a knockout mouse in which all motor neurons leave the spinal cord through the lateral exit points. [unreadable] [unreadable]